Rev is a key regulatory protein of HV-1. Its function is to bind to viral transcripts and effect export from the nucleus of unspliced mRNA thereby allowing the production of structural proteins. Despite its importance, the structure has not been determined due to tendency of the protein to aggregate. Monoclonal antibody antigen binding domains (Fab) can mediate co-crystallization of refractory proteins. A chimeric rabbit/human Fab against Rev was selected by phage display, produced in a bacterial secretion system, and purified from the media. A Fab-Rev complex was produced which generated crystals from which the structure of Rev was determined by X-ray crystallography for the first time. The structure consisted of a molecular dimer of Rev, bound on either side by a Fab, where the ordered portion of each Rev monomer contains two coplanar &#945;-helices arranged in hairpin fashion. Hydrophobic patches on the outer surface of the dimer (blocked by the bound Fab) promote the higher order interactions, suggesting a model for Rev oligomerization onto the viral RNA. The corresponding single chain antibody (scFv) was also prepared, offering the potential of antibody therapeutics against HIV-1. HIV protease, a homodimeric protein is essential in the viral life cycle and a major anti-HIV drug target. Peptides derived from the N- and C-terminal regions of the HIV-1 protease dimer interface inhibit protease activity by preventing dimerization (monomeric protein is inactive). In previous work, it was shown that the solubility and cell permeability of the peptides was enhanced by linking the transduction domain of HIV-Tat. Recently we developed a genetic construct that can be used to study the first step in the cascade of HIV-1 protease Gag-Pro-Pol processing and show that reversible oxidation of cysteines can control the activity of the HIV-1 protease at this initial step. This assay system also has the potential for the screening of potential dimerization inhibitors.